Cellular distribution of the C-type II lectin dendritic cell immunoreceptor (DCIR) and its expression in the rheumatic joint: identification of a subpopulation of DCIR+ T cells

Eklöw, Carina; Makrygiannakis, Dimitrios; Bäckdahl, Liselotte; Padyukov, Leonid; Ulfgren, Ann‐Kristin; Lorentzen, Johnny C.; Malmström, Vivianne

doi:10.1136/ard.2007.076976

Cited by 30 publications

(26 citation statements)

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“…18 In conclusion, our data demonstrate the influence of common variations on the transcription of the DCIR gene, which we also have replicated in an independent material. This indicates the significance of DCIR in immune reactions regulated by IFN-g and related to the development of inflammation.…”

Section: Differential Expression Of Dcirsupporting

confidence: 80%

Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor

et al. 2008

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Dendritic cell immunoreceptor (DCIR) deficiency is related to development of autoimmune disorders and DCIR gene polymorphisms are associated with rheumatoid arthritis (RA). We analyzed the mRNA expression from the four known transcripts of DCIR in IFN-g-treated human leukocytes together with fine mapping across the locus. RA patients and healthy controls were genotyped for several single nucleotide polymorphisms (SNPs) in DCIR and flanking regions. mRNA expression in peripheral blood mononuclear cells (PBMCs), stimulated with gamma-interferon (IFN-g) in vitro, was determined by transcript-specific PCR. Our data reveal that IFN-g significantly downregulates the average expression of transcripts DCIR_v1, DCIR_v2, DCIR_v3 and DCIR_v4 (Po0.0001 for v1, Po0.02 for v2, Po0.0001 for v3, Po0.001 for _v4, patients and controls, Wilcoxon signed-rank). The expression of DCIR showed significant association with variations in the gene. Cells with the RAassociated allele rs2024301 exhibit a significant increase in the expression of DCIR_v4. We also present a new fifth isoform lacking exons 2, 3 and 4. This data illustrate that common genetic variations may influence DCIR mRNA expression. We also show that the expression is regulated by the inflammatory mediator IFN-g, affecting all four transcripts and that this was independent of genotype.

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Section: Differential Expression Of Dcirsupporting

confidence: 80%

Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor

et al. 2008

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“…Therefore, the finding that DCIR plays a major role in limiting CHIKV-induced inflammatory disease represents the first demonstration that a CLR plays a major role in the pathogenesis of alphavirus-induced arthritis. This result is consistent with prior studies which have shown that DCIR polymorphisms are associated with susceptibility to rheumatoid arthritis in humans (46,66,67) and modulate the severity of collagen-induced arthritis in mice (44,62). It is interesting that these studies showed that increased DCIR expression correlates with rheumatoid arthritis occurrence and severity.…”

Section: Discussionsupporting

confidence: 82%

“…However, while the field has also made significant progress in identifying specific host sensing pathways in the detection of CHIKV and subsequent induction of protective interferon responses (28,56,60,61), the role of other host molecules in the pathogenesis of CHIKV-induced disease is still relatively poorly understood. Given that host CLRs likely interact with alphaviruses and since DCIR has been associated with other arthritic diseases (44,46,62), we tested whether DCIR played any role in the pathogenesis of CHIKV-induced disease.…”

Section: Discussionmentioning

confidence: 99%

“…DCIR contains an immunoreceptor tyrosine-based inhibitory motif (ITIM), and evidence from several studies supports its role as an inhibitory receptor (43)(44)(45). Recently, elevated DCIR expression on several cell types was implicated in the chronic inflammation associated with rheumatoid arthritis and myocardial infarction in humans (46) and with mouse models of rheumatoid arthritis (44). Given DCIR's role as a negative regulator of the host inflammatory response and its association with rheumatoid arthritis, we evaluated whether DCIR played a role in the response to CHIKV infection.…”

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Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

Long

Whitmore

Ferris

et al. 2013

J Virol

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c Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for recent epidemic outbreaks of debilitating disease in humans. Alphaviruses are known to interact with members of the C-type lectin receptor family of pattern recognition proteins, and given that the dendritic cell immunoreceptor (DCIR) is known to act as a negative regulator of the host inflammatory response and has previously been associated with rheumatoid arthritis, we evaluated DCIR's role in response to CHIKV infection. Although we observed an increase in the proportion of dendritic cells at the site of CHIKV infection at 24 to 36 h postinfection, these cells showed decreased cell surface DCIR, suggestive of DCIR triggering and internalization. In vitro, bone marrow-derived dendritic cells from DCIR-deficient (DCIR ؊/؊ ) mice exhibited altered cytokine expression following exposure to CHIKV. DCIR ؊/؊ mice exhibited more severe disease signs than wild-type C57BL6/J mice following CHIKV infection, including a more rapid and more severe onset of virus-induced edema and enhanced weight loss. Histological examination revealed that DCIRdeficient animals exhibited increased inflammation and damage in both the fascia of the inoculated foot and the ankle joint, and DCIR deficiency skewed the CHIKV-induced cytokine response at the site of infection at multiple times postinfection. Early differences in virus-induced disease between C57BL6/J and DCIR ؊/؊ mice were independent of viral replication, while extended viral replication correlated with enhanced foot swelling and tissue inflammation and damage in DCIR ؊/؊ compared to C57BL6/J mice at 6 to 7 days postinfection. These results suggest that DCIR plays a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage.

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“…Testing our array of C-type lectin receptors we did not find binding of the antibody clone 260110 or the polyclonal hDCIR serum to another C-type lectin receptor (data not shown), suggesting that other receptors not represented in our library might be recognized. With respect to the identification of soluble versions of hDCIR that might be secreted into the serum of patients with arthritis [24,[30][31], the combination of 15E12 with other commercially available anti hDCIR antibodies might be a useful tool to detect these soluble variants by ELISA (Fig. 5D).…”

Section: Discussionmentioning

confidence: 99%

Efficient generation of a monoclonal antibody against the human C-type lectin receptor DCIR by targeting murine dendritic cells

Heidkamp¹,

Neubert²,

Haertel³

et al. 2010

Immunology Letters

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Dendritic cells (DCs) are very important for the generation of long lasting immune responses against pathogens or the induction of anti-tumor responses. Targeting antigen to dendritic cells via monoclonal antibodies specific for DC cell surface receptors such as DEC205 was shown to elicit potent cellular and humoral immune responses in vivo. Therefore we investigated whether this novel strategy might also be useful for the generation of new monoclonal antibodies against molecules of choice. We show, that by targeting the extracellular domain of the human C-type lectin receptor ClecSF6/DCIR/LLIR (hDCIR) to DEC205 on DCs in vivo, we were able to generate highly specific monoclonal antibodies against hDCIR. Keywordsdendritic cell subsets; DCIR; ClecSF6; monoclonal antibody generation; antibody targeting IntroductionDendritic cells (DCs) are the most important antigen presenting cells. They act as sentinels, take up and process antigens from the periphery such as the skin, airways, intestine, or interstitial spaces of various organs. Besides the uptake of soluble antigens, DCs are also able to ingest apoptotic cells, tumor cells, or infected cells. Antigen loaded DCs migrate from the periphery to the lymphoid tissues where they interact with antigen-specific T cells to present their antigens [1].Antigen uptake is mediated either by macropinocytosis, phagocytosis or receptor mediated endocytosis followed by presentation of antigen derived peptides on major histocompatibility class I (MHC I) and II (MHC II) molecules to T cells [2][3][4]. Recently, this highly efficient antigen uptake and antigen presentation capacity of DCs has been used * Corresponding author. Tel.: +49 9131 85 39346; Fax: +49 9131 85 39347. diana.dudziak@uk-erlangen.de (D. Dudziak). The other authors have no conflicting financial interests.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscriptto initiate cellular and humoral immune responses against a variety of model antigens. To deliver the antigen to dendritic cells in vivo the antigen was fused to monoclonal antibodies recognizing endocytic cell surface receptors expressed on dendritic cells including the Ctype lectin receptor DEC205 (CD205), DC-inhibitory receptor 2 (DCIR2), DC-NK lectin group receptor 1 (DNGR-1/Clec9a), CD11c, MHC-II and CD207 (Langerin) [5][6][7][8][9][10]. [11][12][13]. The potency of this strategy is reflected by the induction of tumor-, virus-and parasitespecific T cell responses upon targeting of the respective antigens to the C-type lectin receptor DEC205 in vivo [10,...

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Cellular distribution of the C-type II lectin dendritic cell immunoreceptor (DCIR) and its expression in the rheumatic joint: identification of a subpopulation of DCIR+ T cells

Cited by 30 publications

References 32 publications

Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor

Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor

Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

Efficient generation of a monoclonal antibody against the human C-type lectin receptor DCIR by targeting murine dendritic cells

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